Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial
We report results of a phase 2, randomized, multicenter, open‐label, two‐arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody‐ mediated rejection (AMR) in sensitized recipients of living‐donor kidney transplants requiring pretransplant desensitization (NCT01399593). In total, 102 patients under‐ went desensitization. Posttransplant, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplant treat‐ ment failure rate, a composite of: biopsy‐proven acute AMR (Banff 2007 grade II or III; assessed by blinded central pathology); graft loss; death; or loss to follow‐up. Eculizumab was well tolerated with no new safety concerns. No significant difference in treatment failure rate was observed between eculizumab (9.8%) and SOC (13.7%; P = .760). To determine whether data assessment assumptions affected study out‐ come, biopsies were reanalyzed by central pathologists using clinical information. The resulting treatment failure rates were 11.8% and 21.6% for the eculizumab and SOC groups, respectively (nominal P = .288). When reassessment included grade I AMR, the treatment failure rates were 11.8% (eculizumab) and 29.4% (SOC; nominal P = .048). This finding suggests a potential benefit for eculizumab compared with SOC in preventing acute AMR in recipients sensitized to their living‐donor kidney transplants (EudraCT 2010‐019630‐28).
|Keywords||clinical research/practice, complement biology, donors and donation: living, immunosuppressant ‐ fusion proteins and monoclonal antibodies, kidney transplantation/ nephrology, rejection: antibody‐mediated (ABMR), sensitization|
|Persistent URL||dx.doi.org/10.1111/ajt.15364, hdl.handle.net/1765/120471|
|Journal||American Journal of Transplantation|
Marks, WH, Mamode, N, Montgomery, R.A., Stegall, M.D., Ratner, LE, Cornell, L.D., … Glotz, D. (2019). Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. American Journal of Transplantation, 19(10), 2876–2888. doi:10.1111/ajt.15364